Emerging novel sequence types of Staphylococcus aureus in Pakistan.

BACKGROUND: Despite an increasing incidence of Staphylococcus aureus infection and dissemination in Pakistan, the epidemiology of different Staphylococcus aureus research clones has been the subject of only a small number of investigations. By analyzing the collected data sequence, this study was designed to study the epidemiology of Staphylococcus aureus in the area using multilocus sequence typing (MLST). METHODS: A total of 1015 staphylococcus strains collected from the city's tertiary care facilities were biochemically screened, followed by antimicrobial susceptibility testing against a panel of 13 antibiotics. Analyzed methicillin-resistant Staphylococcus aureus (MRSA) was subjected to molecular characterization using multilocus sequence typing (MLST), clonal complex analysis, recombination testing, and phylogenetic analysis. RESULTS: Approximately 421 bacteria were verified as Staphylococcus aureus by biochemical analysis. 57% of the isolates exhibited multidrug resistance, of which 89% were found to be methicillin-resistant Staphylococcus aureus (MRSA). MLST results in a total of 39 sequence types (ST) and 5 clonal complexes (CC), out of which twenty-two STs were newly documented worldwide. The most common CC identified was CC8. The direct sequencing data also revealed significant shifts at MLST loci, with point mutations resulting in the aroE-343 and tpi-278 alleles. CONCLUSIONS: This study concludes that there is high diversity in the locally circulating clones of Staphylococcus aureus present in nature and that they are defined by their geographic epidemiology. These findings have practical implications for public health, including the need for tailored infection control strategies, antibiotic stewardship, global surveillance, and a deeper understanding of bacterial evolution.

COVID-19 Lockdown in New Zealand: Perceived Stress and Wellbeing among International Health Students Who Were Essential Frontline Workers.

This study examined the stresses and wellbeing of international postgraduate health and nursing students at a tertiary education institute in New Zealand who were mainly essential frontline healthcare workers during the COVID-19 lockdown. Quantitative and qualitative data were collected by purposeful sampling (n = 43). The study utilised a cross-sectional survey, along with the Short Form of Cohen's Perceived Stress Scale (PSS-10), adapted for the COVID-19 lockdown, and followed by semi-structured individual interviews. This study is the first in New Zealand to demonstrate that, with a mean PSS-10 score of 21.7 (±7.1), international health students experienced higher than optimal levels of stress, with supporting qualitative data identifying four themes for the sources of stress: (1) familial relationships, (2) essential work, (3) finances, and (4) study. However, these students coped because of the extensive support provided by their education institute and employers. These students played a critical role in the pandemic's response and made a significant public health contribution by working in the frontline of the COVID-19 outbreak. Considering the global shortage of healthcare workers and understanding the key challenges, means of coping and support provisions, as we have here, offer insights for building and maintaining a resilient and resourceful health workforce through international health and nursing students in New Zealand and elsewhere.

Barriers and drivers in mental health services in New Zealand: current status and future direction.

In New Zealand, mental health issues have created a 'silent epidemic' with diverse consequences in mental health outcomes. Poor mental health state along with inequities to access services are persistent. Key areas of mental health promotion in New Zealand that require constant attention are appropriate policymaking, reaching out to all communities, interventions at the individual level, and the complexity of the mental health system. This commentary evaluates the inadequacies faced by the public in accessing mental health services and the directions to improve in the future. It also reviews the New Zealand government's 'Like Mind, Like Mine' program, aiming to provide socially inclusive services to people to live a life free from mental health-related stigma or discrimination.

Effect of salicylic acid supplementation on blood glucose, lipid profile and electrolyte homeostasis in gentamicin sulphate induced nephrotoxicity.

This study was designed to investigate effect of salicylic acid supplementation in gentamicin- induced nephrotoxicity. For this purpose, twenty four male albino rabbits were divided into 4 groups (n=6); control group, healthy untreated rabbits; gentamicin group, received only gentamicin (80mg/kg); gentamicin + salicylic acid group, received gentamicin (80mg/kg) + salicylic acid (80mg/kg) and salicylic acid group, received only salicylic acid (80mg/kg) through intra peritoneal route for 21 consecutive days. Biochemical evaluation was carried out by assessment of body weights and by estimating plasma glucose, lipid profile and electrolyte homeostasis. Gentamicin sulphate induction resulted in increased plasma glucose, plasma TG, plasma cholesterol, plasma LDL, and plasma sodium and in decreased plasma HDL and plasma potassium with significant reduction in body weights in GS-treated group, which were restored by supplementation with salicylic acid in GS+SA treated group. Therefore, these findings confirm the protective role of salicylic acid in gentamicin- induced nephrotoxicity in rabbits.

Possible association of Vitamin D receptor, caudal-related homeobox 2 polymorphism with the risk of cancer.

OBJECTIVE: This study was conducted to find out the possible association of Vitamin D receptor, caudal-related homeobox 2 (VDR-Cdx2) polymorphism with cancer in the given study group. METHODS: In this study, 151 subjects (84 cases and 67 controls) were recruited from two local tertiary care hospitals of Karachi, Pakistan, suffering from various cancers including gastric cancer (GC), rectal cancer (RC), colon cancer (CC), and multiple myeloma followed by ethical approval from institutions and informed consent from all the participants. The genotyping of VDR-Cdx2 polymorphism was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The genotypic assortment/distribution in the control and disease groups was according to Hardy-Weinberg's equilibrium. RESULTS: The genotype frequencies of VDR-Cdx2 polymorphism in cancer patients were observed as: AA 1.2%, AG 32%, and GG 66.8% while in control group as; AA 7.5%, AG 50.7%, and GG was 41.8%. The results unveil that the genotype VDR-Cdx2 was found significantly different in cancer and control group (P < 0.01). The AG and GG genotypes were found to be associated with the cancer (P < 0.05). Therefore, these genotypes may be considered as the risk factors for cancer. However, the frequencies of "A" and "G" alleles were not significantly different between two groups. CONCLUSION: The observed single-nucleotide polymorphism of VDR-Cdx2 gene may be considered as a risk factor for the cancer in this study group. The AG and GG genotypes established an association with various cancers including GC, RC, CC, and multiple myeloma in Pakistani population. Further investigations examining large data are required to compare the role of VDR-Cdx2 polymorphism in cancer etiology in related population.

Development of a Piezoelectric PVDF-TrFE Fibrous Scaffold to Guide Cell Adhesion, Proliferation, and Alignment.

Severe peripheral nervous system injuries currently hold limited therapeutic solutions. Existing clinical techniques such as autografts, allografts, and newer nerve guidance conduits have shown variable outcomes in functional recovery, adverse immune responses, and in some cases low or minimal availability. This can be attributed in part to the lack of chemical, physical, and electrical cues directing both nerve guidance and regeneration. To address this pressing clinical issue, electrospun nanofibers and microfibers composed of piezoelectric polyvinylidene flouride-triflouroethylene (PVDF-TrFE) have been introduced as an alternative template for tissue engineered biomaterials, specifically as it pertains to their relevance in soft tissue and nerve repair. Here, biocompatible scaffolds of PVDF-TrFE are fabricated and their ability to generate an electrical response to mechanical deformations and produce a suitable regenerative microenvironment is examined. It is determined that 20% (w/v) PVDF-TrFE in (6:4) dimethyl formamide (DMF):acetone solvent maintains a desirable piezoelectric coefficient and the proper physical and electrical characteristics for tissue regeneration. Further, it is concluded that scaffolds of varying thickness promoted the adhesion and alignment of Schwann cells and fibroblasts. This work offers a prelude to further advancements in nanofibrous technology and a promising outlook for alternative, autologous remedies to peripheral nerve damage.

Comprehensive Approaches to Improving Nutrition: Future Prospects.

When it comes to nutrition, nearly everyone has an opinion. In the past, nutrition was considered to be an individual's responsibility, however, more recently governments have been expected (by some) to share that responsibility by helping to ensure that marketing is responsible, and that food chains offer healthy meal choices in addition to their standard fare, for example. In some countries, governments have gone as far as to remove tax from unprocessed foods or to introduce taxes, such as that imposed on sugary soft drinks in the UK, Mexico, France and Norway. Following on from the sugar tax, chocolate might be next! Is this the answer to our burgeoning calorie intake and increasing poor nutritional status, or is there another approach? In this narrative we will focus on some of the approaches taken by communities and governments to address excess calorie intake and improve nutritional status, as well as some of the conflicts of interest and challenges faced with implementation. It is clear that in order to achieve meaningful change in the quality of nutritional intake and to reduce the long-term prevalence of obesity, a comprehensive approach is required wherein governments and communities work in genuine partnership. To take no or little action will doom much of today's youth to a poor quality of life in later years, and a shorter life expectancy than their grandparents.

Aggressive prostate cancer incidence in New Zealand-"united we fall, divided we stand".

Prostate cancer is an important health burden to the healthcare system of any country. However, with the current prostate-specific antigen biomarker having low predictive value even for diagnostic purposes, the challenge is still open to tackle this chronic disease. There have been a number of studies which have indicated and encouraged a multi-directional approach to combat this disease. We have been carrying out a multi-directional approach in order to identify certain New Zealand-specific factors which may be drivers for this cancer and its aggressive forms. These will be explained in further detail in this research letter.

Genetic variants of ACE (Insertion/Deletion) and AGT (M268T) genes in patients with diabetes and nephropathy.

INTRODUCTION: Diabetes mellitus (DM) has been a growing epidemic worldwide and poses a major socio-economic challenge. The leading cause of DM death is nephropathy due to end-stage renal disease (ESRD). This study aims to identify the possible association of I/D variants of the ACE gene and M268T (rs699) of the AGT gene of renin-angiotensin-aldosterone system (RAAS). MATERIALS AND METHODS: Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN) and 110 controls. Fasting blood samples were collected for biochemical analyses and PCR amplification of specific regions of the ACE and AGT genes using primers. RESULTS: The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and MM 0.9%. CONCLUSION: Significant differences were observed in the DD genotype and D allele of the ACE gene and the TT genotype and T allele of AGT genes between diabetic patients with and without nephropathy. The study may conclude that the D allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may be considered as genetic risk factors for the development of nephropathy in diabetes.

Sudden apparent worsening of diabetic retinopathy leading to a diagnosis of chronic myeloid leukaemia.

A 65-year-old woman with well-controlled type 2 diabetes presented with a sudden decrease in visual acuity bilaterally (right eye 6/60, left eye 6/18).

Phylogenetic analysis of HDV isolates from HBsAg positive patients in Karachi, Pakistan.

BACKGROUND: In spite of a high occurrence of Hepatitis Delta in the province of Sindh in Pakistan, no genetic study of Hepatitis Delta virus (HDV) isolates from this region was carried out. The aim of this study is to analyze the genetic proximity within local HDV strains, and relationship with other clades of HDV, using phylogenetic analysis. RESULTS: Phylogenetic analysis of nucleotide sequences of the Hepatitis Delta Antigen (HDAg) R0 region obtained in this study, showed considerable diversity among the local strains with a potential subgroup formation within clade I. The multiple sequence alignment of predicted amino acids within clade I showed many uncommon amino acid substitutions within some conserved regions that are crucial for replication and assembly of HDV. CONCLUSIONS: The studied strains showed a range of genetic diversity within HDV clade I. There is clustering of sequences into more than one group, along with formation of potential subgroup within clade I. Clustering shows the genetic closeness of strains and indicates a common origin of spread of HDV infection. Further phylogeny-based studies may provide more information about subgroup formation within clade I and may be used as an effective tool in checking and/or preventing the spread of hepatitis D virus infection in this region.

Protective effects of salivary factors in dental caries in diabetic patients of Pakistan.

Salivary factors have been studied for their effects on the process of dental caries in patients of diabetes mellitus type 2. In this study, protective role of salivary pH, salivary flow rate, and salivary calcium is assessed in the patients of diabetes mellitus type 2 with dental caries. The samples of saliva were collected from 400 patients of diabetes mellitus type 2 and 300 age- and sex- matched controls after getting informed consent. All the subjects were classified into four groups according to age. The severity of dental caries was counted by decayed, missed, and filled teeth (DMFT) score. The salivary pH, flow rate, and calcium levels were found to be low in patients as compared to controls. The levels of fasting blood sugar, HbA1c, and DMFT score were found to be significantly high in patients than controls. The glycemic factors were significantly correlated with salivary factors indicating their influence on progression of caries in diabetes. On the basis of findings, it is concluded that the suitable salivary pH and flow rate may be regarded as main protective factors against dental caries in diabetes. Optimum level of salivary calcium may be responsible for continuous supply of calcium to arrest the demineralization and help reduce the occurrence of dental caries.

Dental caries in diabetes mellitus: role of salivary flow rate and minerals.

This study was designed to evaluate the possible protective role of salivary factors like salivary flow rate and adequate level of calcium, phosphate, and fluoride in diabetes mellitus type 2 patients with dental caries. A total of 398 diabetes mellitus type 2 patients with dental caries and 395 age- and sex-matched non-diabetic subjects with dental caries were included as controls, all of whom gave informed consent. All subjects were divided into four groups according to their age. Decayed, missed, and filled teeth (DMFT) were scored to indicate the severity of dental caries. Saliva was collected, flow rate was noted, and calcium, phosphate, and fluoride were analyzed. The blood glucose, HbA1c, and DMFT indices were found to be significantly high in diabetic patients as compared to controls. The salivary flow rate, calcium, phosphate, and fluoride were found to be significantly low whereas no significant difference was found in salivary magnesium in patients as compared to controls. Optimum salivary flow rate is responsible for establishing protective environment against dental caries. Adequate level of salivary calcium, phosphate, and fluoride is also involved in significant deposition of these minerals in plaque, which greatly reduces the development of caries in the adjacent enamel of teeth.

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis.

BACKGROUND: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan. MAIN OBSERVATIONS: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced. Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids). CONCLUSION: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.